Engineering particles for therapeutic delivery: prospects and challenges.

Nanoengineered particles that can facilitate drug formulation and passively target tumors have reached the clinic in recent years. These early successes have driven a new wave of significant innovation in the generation of advanced particles. Recent developments in enabling technologies and chemistries have led to control over key particle properties, including surface functionality, size, shape, and rigidity. Combining these advances with the rapid developments in the discovery of many disease-related characteristics now offers new opportunities for improving particle specificity for targeted therapy. In this Perspective, we summarize recent progress in particle-based therapeutic delivery and discuss important concepts in particle design and biological barriers for developing the next generation of particles.

[1]  Louis M. Weiner,et al.  Monoclonal antibodies: versatile platforms for cancer immunotherapy , 2010, Nature Reviews Immunology.

[2]  Philip S Low,et al.  Discovery and development of folic-acid-based receptor targeting for imaging and therapy of cancer and inflammatory diseases. , 2008, Accounts of chemical research.

[3]  A. Scott,et al.  A phase I clinical trial with monoclonal antibody ch806 targeting transitional state and mutant epidermal growth factor receptors , 2007, Proceedings of the National Academy of Sciences.

[4]  H. McMahon,et al.  Mechanisms of endocytosis. , 2009, Annual review of biochemistry.

[5]  Mark E. Davis,et al.  Evidence of RNAi in humans from systemically administered siRNA via targeted nanoparticles , 2010, Nature.

[6]  Daniel W. Pack,et al.  Design and development of polymers for gene delivery , 2005, Nature Reviews Drug Discovery.

[7]  K. Landfester,et al.  Uptake mechanism of oppositely charged fluorescent nanoparticles in HeLa cells. , 2008, Macromolecular bioscience.

[8]  Dan Peer,et al.  Reshaping the future of nanopharmaceuticals: ad iudicium. , 2011, ACS nano.

[9]  Shiroh Futaki,et al.  High Density of Octaarginine Stimulates Macropinocytosis Leading to Efficient Intracellular Trafficking for Gene Expression* , 2006, Journal of Biological Chemistry.

[10]  Robert Langer,et al.  Nanoparticle delivery of cancer drugs. , 2012, Annual review of medicine.

[11]  S. MacNeil,et al.  Biomimetic pH Sensitive Polymersomes for Efficient DNA Encapsulation and Delivery , 2007 .

[12]  Silvia Muro,et al.  Endothelial targeting of antibody-decorated polymeric filomicelles. , 2011, ACS nano.

[13]  Samir Mitragotri,et al.  Role of target geometry in phagocytosis. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[14]  Mauro Ferrari,et al.  Nanomedicine in cancer therapy: Innovative trends and prospects , 2011, Cancer science.

[15]  P. Grutter,et al.  Effect of mechanical properties of hydrogel nanoparticles on macrophage cell uptake , 2009 .

[16]  S. Nguyen,et al.  "Clickable" polymer-caged nanobins as a modular drug delivery platform. , 2009, Journal of the American Chemical Society.

[17]  Darrell J Irvine,et al.  Cytosolic delivery of membrane-impermeable molecules in dendritic cells using pH-responsive core-shell nanoparticles. , 2007, Nano letters.

[18]  F. Caruso,et al.  The Role of Particle Geometry and Mechanics in the Biological Domain , 2012, Advanced healthcare materials.

[19]  T. Fujiwara,et al.  Intracellular fate of octaarginine-modified liposomes in polarized MDCK cells. , 2010, International journal of pharmaceutics.

[20]  Pedro M. Valencia,et al.  Targeted Polymeric Therapeutic Nanoparticles: Design, Development and Clinical Translation , 2012 .

[21]  Warren C W Chan,et al.  Nanoparticle-mediated cellular response is size-dependent. , 2008, Nature nanotechnology.

[22]  Ceirin M. Connolly-Ingram,et al.  Development of a highly stable and targetable nanoliposomal formulation of topotecan. , 2010, Journal of controlled release : official journal of the Controlled Release Society.

[23]  Stephanie E. A. Gratton,et al.  The effect of particle design on cellular internalization pathways , 2008, Proceedings of the National Academy of Sciences.

[24]  D. Jans,et al.  Nucleocytoplasmic transport of DNA: enhancing non-viral gene transfer. , 2007, The Biochemical journal.

[25]  Omid C Farokhzad,et al.  Targeted polymeric therapeutic nanoparticles: design, development and clinical translation. , 2012, Chemical Society reviews.

[26]  S. Futaki,et al.  Octaarginine- and Octalysine-modified Nanoparticles Have Different Modes of Endosomal Escape* , 2008, Journal of Biological Chemistry.

[27]  Frank Caruso,et al.  Targeting of cancer cells using click-functionalized polymer capsules. , 2010, Journal of the American Chemical Society.

[28]  D. Discher,et al.  Shape effects of filaments versus spherical particles in flow and drug delivery. , 2007, Nature nanotechnology.

[29]  R. China,et al.  The CD 47-signal regulatory protein alpha ( SIRPa ) interaction is a therapeutic target for human solid tumors , 2012 .

[30]  Jens-Peter Volkmer,et al.  The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors , 2012, Proceedings of the National Academy of Sciences.

[31]  I. Zuhorn,et al.  Size-dependent internalization of particles via the pathways of clathrin- and caveolae-mediated endocytosis. , 2004, The Biochemical journal.

[32]  Lloyd J. Old,et al.  Phase I Trial of 131I-huA33 in Patients with Advanced Colorectal Carcinoma , 2005, Clinical Cancer Research.

[33]  R. Jain,et al.  Delivering nanomedicine to solid tumors , 2010, Nature Reviews Clinical Oncology.

[34]  A. Krainer,et al.  RNA therapeutics: beyond RNA interference and antisense oligonucleotides , 2012, Nature Reviews Drug Discovery.

[35]  A. Scott,et al.  Phase I Trial of 131 I-huA 33 in Patientswith Advanced Colorectal Carcinoma , 2005 .